Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 µ/L and it was completely eliminated after 96 h.

Assessment of the potential of tin sulphide thin films prepared by sulphurization of metallic precursors as cell absorbers

In this work, SnxSy thin films have been grown on soda-lime glass substrates by sulphurization of metallic precursors in a nitrogen plus sulphur vapour atmosphere. Different sulphurization temperatures were tested, ranging from 300 °C to 520 °C. The resulting phases were structurally investigated by X-Ray Diffraction and Raman spectroscopy. Composition was studied using Energy Dispersive Spectroscopy being then correlated with the sulphurization temperature. Optical measurements were performed to obtain transmittance and reflectance spectra, from which the energy band gaps, were estimated. The values obtained were 1.17 eV for the indirect transition and for the direct transition the values varied from 1.26 eV to 1.57 eV. Electrical characterization using Hot Point Probe showed that all samples were p-type semiconductors. Solar cells were built using the structure: SLG/Mo/SnxSy/CdS/ZnO:Ga and the best result for solar cell efficiency was 0.17%.

Histamine induces ATP release from human subcutaneous fibroblasts via pannexin-1 hemichannels leading to Ca2+ mobilization and cell proliferation

Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca2+ ([Ca2+]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca2+]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca2+]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with 10Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca2+]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADPsensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca2+]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.

Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder

Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets

Timing analysis of an inter-cell mobility procedure for a wired/wireless PROFIBUS network

Recently, there have been a few research efforts towards extending the capabilities of fieldbus networks to encompass wireless support. In previous works we have proposed a hybrid wired/wireless PROFIBUS network solution where the interconnection between the heterogeneous communication media was accomplished through bridge-like interconnecting devices. The resulting networking architecture embraced a Multiple Logical Ring (MLR) approach, thus with multiple independent tokens, where the communication between different domains was supported by the Inter-Domain Protocol (IDP). The proposed architecture also supports mobility of stations between different wireless cells. To that hybrid wired/wireless networking architecture we have proposed a worst-case response timing analysis of the IDP, without considering inter-cell mobility (or handoff) of stations. In this paper, we advance that previous work by proposing a worst-case timing analysis of the mobility procedure.

Profibus protocol extensions for enabling inter-cell mobility in bridge-based hybrid wired/wireless networks

Future industrial control/multimedia applications will increasingly impose or benefit from wireless and mobile communications. Therefore, there is an enormous eagerness for extending currently available industrial communications networks with wireless and mobility capabilities. The RFieldbus European project is just one example, where a PROFIBUS-based hybrid (wired/wireless) architecture was specified and implemented. In the RFieldbus architecture, interoperability between wired and wireless components is achieved by the use specific intermediate networking systems operating at the physical layer level, i.e. operating as repeaters. Instead, in this paper we will focus on a bridge-based approach, which presents several advantages. This concept was introduced in (Ferreira, et al., 2002), where a bridge-based approach was briefly outlined. Then, a specific Inter-Domain Protocol (IDP) was proposed to handle the Inter-Domain transactions in such a bridge-based approach (Ferreira, et al., 2003a). The major contribution of this paper is in extending these previous works by describing the protocol extensions to support inter-cell mobility in such a bridge-based hybrid wired/wireless PROFIBUS networks.

Besnoitia besnoiti and Toxoplasma gondii: two apicomplexan strategies to manipulate the host cell centrosome and Golgi apparatus

Besnoitia besnoiti and Toxoplasma gondii are two closely related parasites that interact with the host cell microtubule cytoskeleton during host cell invasion. Here we studied the relationship between the ability of these parasites to invade and to recruit the host cell centrosome and the Golgi apparatus. We observed that T. gondii recruits the host cell centrosome towards the parasitophorous vacuole (PV), whereas B. besnoiti does not. Notably, both parasites recruit the host Golgi apparatus to the PV but its organization is affected in different ways. We also investigated the impact of depleting and over-expressing the host centrosomal protein TBCCD1, involved in centrosome positioning and Golgi apparatus integrity, on the ability of these parasites to invade and replicate. Toxoplasma gondii replication rate decreases in cells over-expressing TBCCD1 but not in TBCCD1-depleted cells; while for B. besnoiti no differences were found. However, B. besnoiti promotes a reorganization of the Golgi ribbon previously fragmented by TBCCD1 depletion. These results suggest that successful establishment of PVs in the host cell requires modulation of the Golgi apparatus which probably involves modifications in microtubule cytoskeleton organization and dynamics. These differences in how T. gondii and B. besnoiti interact with their host cells may indicate different evolutionary paths.

Software transactional memory as a building block for parallel embedded realtime systems

The recent trends of chip architectures with higher number of heterogeneous cores, and non-uniform memory/non-coherent caches, brings renewed attention to the use of Software Transactional Memory (STM) as a fundamental building block for developing parallel applications. Nevertheless, although STM promises to ease concurrent and parallel software development, it relies on the possibility of aborting conflicting transactions to maintain data consistency, which impacts on the responsiveness and timing guarantees required by embedded real-time systems. In these systems, contention delays must be (efficiently) limited so that the response times of tasks executing transactions are upper-bounded and task sets can be feasibly scheduled. In this paper we assess the use of STM in the development of embedded real-time software, defending that the amount of contention can be reduced if read-only transactions access recent consistent data snapshots, progressing in a wait-free manner. We show how the required number of versions of a shared object can be calculated for a set of tasks. We also outline an algorithm to manage conflicts between update transactions that prevents starvation.

WCET analysis considering contention on memory bus in COTS-based multicores

The usage of COTS-based multicores is becoming widespread in the field of embedded systems. Providing realtime guarantees at design-time is a pre-requisite to deploy real-time systems on these multicores. This necessitates the consideration of the impact of the contention due to shared low-level hardware resources on the Worst-Case Execution Time (WCET) of the tasks. As a step towards this aim, this paper first identifies the different factors that make the WCET analysis a challenging problem in a typical COTS-based multicore system. Then, we propose and prove, a mathematically correct method to determine tight upper bounds on the WCET of the tasks, when they are co-scheduled on different cores.

Response time analysis of COTS-Based multicores considering the contention on the shared memory bus

The current industry trend is towards using Commercially available Off-The-Shelf (COTS) based multicores for developing real time embedded systems, as opposed to the usage of custom-made hardware. In typical implementation of such COTS-based multicores, multiple cores access the main memory via a shared bus. This often leads to contention on this shared channel, which results in an increase of the response time of the tasks. Analyzing this increased response time, considering the contention on the shared bus, is challenging on COTS-based systems mainly because bus arbitration protocols are often undocumented and the exact instants at which the shared bus is accessed by tasks are not explicitly controlled by the operating system scheduler; they are instead a result of cache misses. This paper makes three contributions towards analyzing tasks scheduled on COTS-based multicores. Firstly, we describe a method to model the memory access patterns of a task. Secondly, we apply this model to analyze the worst case response time for a set of tasks. Although the required parameters to obtain the request profile can be obtained by static analysis, we provide an alternative method to experimentally obtain them by using performance monitoring counters (PMCs). We also compare our work against an existing approach and show that our approach outperforms it by providing tighter upper-bound on the number of bus requests generated by a task.